Replacement arthroplasty, or joint replacement surgery, is a form of orthopaedic surgery involving the musculoskeletal system wherein joint or joint surface tissue is replaced with a prosthesis, often used to treat or alleviate symptoms associated with, or caused by, musculoskeletal trauma, sports injuries, degenerative diseases, infections, tumours, and congenital disorders. One such example is the hip joint that is affected by osteoarthritis. It may be replaced entirely (total hip arthroplasty) with a prosthetic hip. The procedure involves replacing both the acetabulum (hip socket) and the head and neck of the femur. The purpose of performing this surgery is to relieve pain, to restore range of motion and to improve walking ability, leading to the improvement of muscle strength.
Joint replacement surgery, however, is often considered as a last option when the severe joint pain or dysfunction experienced by the patient is no longer alleviated by less-invasive therapies. This intervention is mainly late-stage due to the medical and intra-operative risks associated with such a major form of surgery, but also more immediate risks such as joint dislocation, loss of motion and weakness, and infection. Additionally, loosening of the prosthetic components may give rise to long term problems where the component moves inside the bone causing pain, which may also result in fragments of wear that can cause an inflammatory reaction and bone absorption (osteolysis).
In an attempt to overcome some of these issues, it is common practice to use bone cements to anchor artificial joints. The bone cement fills the free space between the prosthesis and the bone and performs the important role of an elastic zone reducing stress concentrations that may arise. A common bone cement is poly(methyl methacrylate) (PMMA), which has been used since the 1950s as a self-setting polymer to improve the fixation of prosthetic implants in orthopaedics, in particular knee and hip arthroplasty. More recently bone cement has been used in the spine in either vertebroplasty or kyphoplasty procedures. Bone cement is considered a reliable anchorage material. It is easy to use in clinical practice and has a proven long survival rate when used with cemented-in prostheses. A prosthetic fixed with bone cement offers very high primary stability combined with fast remobilization of patients. The cemented-in prosthesis can be fully loaded very soon after the operation, and the necessary rehabilitation is comparatively simple for those patients.
However, as stated, a problem that can occur as a consequence of orthopaedic surgery is bacterial colonisation, leading to infections and inflammatory responses which are known to result in the eventual failure of the implant. To overcome this problem, antibiotics can be added to the cement. The antibiotics, advantageously, are released locally after implant placement without subjecting the body in general to unnecessarily high antibiotic levels. The use of antibiotics in this way has been confirmed to reduce the danger of infection. Antibiotic cements are also advantageously used when replacing implants that have previously become infected. Temporary PMMA spacers containing antibiotics can also be employed when replacing infected implants.
When making commercially available bone cements antibiotics are mixed in a powdered form with the cement mixture. This method, although widely adopted, has several key disadvantages. For instance, when using bone cements impregnated with antibiotics, consideration must be given to the release profile of the antibiotic from the cement into the surrounding tissue; too much powdered antibiotic in the bone cement can actually be detrimental, due to weakening of the mechanical stability of the fixed prosthesis. It is also known that powdered antibiotic has a tendency to agglomerate, resulting in stress concentrations, and leaving large pores when the antibiotic is released that are detrimental to the structural integrity of the cement. Additionally, this common method of incorporation has been shown to exhibit poor release profiles, typically with high release of antibiotic shortly after implantation which then drastically and disadvantageously reduces post-surgery.
For example, typical antibiotics used in cements are the aminoglycosides, such as gentamicin sulphate, which are loaded into the cement at high concentrations (typically 0.5 g to 1 g per 40 g of PMMA bone cement). These high concentrations can lead to increased costs and also weakening of the cement, reducing its mechanical properties. Although large quantities of the antibiotic are introduced into the cement, only fractions of it are released into the surrounding tissue (0-10%) and this mostly occurs within the first 6 hours of implantation. This is caused by the diffusion of antibiotic from the surface of the cement only, leaving the bulk of the antibiotic deeper in the cement mantle.
We describe herein a novel antibiotic delivery vehicle for delivering and dispersing antibiotic in bone cement such that the resultant product exhibits uniform mixing of antibiotic in the cement thus having an improved antibiotic release profile and surprising structural advantages without compromising the mechanical strength and/or fatigue properties of the cement.